The present invention concerns a system for treating a cardiovascular disorder by artificial neural stimulation. More particularly, it relates to an implantable medical device configured to provide both chemical and electrical stimulation of one or more nerves of a patient, causing regulation of the heart, vasculature and other bodily systems.
A variety of different cardiovascular ailments relate to, or are caused by, abnormal blood pressure regulation. In general terms, the heart functions to pump blood containing oxygen and nutrients to bodily tissues and organs. Blood being pumped to and from the heart develops a pressure (or blood pressure) in the heart and arteries. Blood pressure is determined by cardiac output and peripheral vascular resistance. The cardiac output, in turn, is a function of heart rate and stroke volume.
Given the above, treatment of abnormal blood pressure-related cardiovascular disorders, such as hypertension and congestive heart failure, focus upon adjusting heart rate, stroke volume, peripheral vascular resistance, or a combination thereof. With respect to heart rate, one area of particular interest is vagal control. The rate of the heart is restrained by vagus nerves in conjunction with cardiac depressor nerves. The vagus nerves extend from the medulla and innervate the heart (as well as other organs). The medulla, in turn, regulates sympathetic and parasympathetic nervous system output, and can affect heart rate in part by controlling vagus nerve activity (or vagal tone) to the heart. The medulla exerts this autonomic control over the heart in response to sensed changes in blood pressure. More particularly, a series of pressure sensitive nerve endings, known as baroreceptors, are located along the carotid sinus, a dilated area at the bifurcation of the common carotid artery. The baroreceptors are formed at the terminal end of the carotid sinus nerve (or Hering's nerve), which is a branch of the glossopharyngeal nerve. The glossopharyngeal nerve extends to the medulla such that the carotid sinus baroreceptors communicate (or signal) with the medulla with carotid sinus pressure information. A reflex pathway (or baroreflex) is thereby established, with the medulla automatically causing an adjustment in heart rate in response to a pressure change in the carotid sinus. For example, a rise in carotid sinus pressure causes the medulla to increase vagal neuronal activity. The above-described reflex pathway (or baroreflex) results in a lowering of the heart rate, and therefore blood pressure. A similar relationship is found with myocardial baroreceptors on the aortic arch. Notably, bodily systems other than the heart, such as the systemic vasculature and kidneys, are also influenced by nerve stimulation and contribute to overall cardiovascular regulation. In light of this vagally-mediated, baroreflex control of heart rate and other bodily systems, it may be possible to regulate heart rate, and thus blood pressure, by artificially stimulating the carotid sinus nerves, myocardial nerves, or other cardiovascular influencing nerves.
One available technique for providing artificial neural stimulation entails implanting an electrode into direct contact with a portion of a selected nerve. A separate, battery-powered activation source or triggering device is likewise implanted and connected to the electrode. The electrode is periodically activated by the triggering device, thereby stimulating the nerve in question and prompting a baroreflex decrease in heart rate. Essentially, activation of the electrode serves to simulate a rise in blood pressure, causing the baroreflex reduction in heart rate. One example of an implantable electrical nerve stimulator is provided in U.S. Pat. No. 5,199,428 assigned to Medtronic, Inc. of Minneapolis, Minn.
While electrical neural stimulation has proven to be a highly viable therapy, certain disadvantages may arise. For example, the battery associated with the triggering device has a finite life, and will inevitably require replacement. Further, in order to achieve adequate nerve stimulation, the frequency, amplitude and/or duration of electrode activation may rise to a level whereby surrounding muscle tissue is also affected, potentially leading to patient discomfort. Finally, it is possible that the nerve will become "desensitized" to the electrical stimulation, requiring increased activation levels and/or duration's, again contributing to patient discomfort and reduced battery life.
As an alternative to electrical stimulation, efforts have been made to identify acceptable chemical compounds formulated to artificially prompt baroreflex control of heart rate, vasculature and other bodily systems. One potentially applicable class of compounds is veratrum alkaloids. Veratrum alkaloids constitute a large group of steroid-like polycyclic nitrogen-containing ring structures found in any of the veratrum species. Two known preparations of veratrum are "veratrum viride" from Veratrum viride, and "veratrum album" from Veratrum album. Further research has identified certain other veratrum alkaloids, such as protoveratrine and veratridine, as being more capable of eliciting the reflex decrease in heart rate and blood pressure. Meilman, E., et al., "Clinical Studies On Veratrum Alkaloids", Circulation 1:204-213 (1950). Meilman et al. and others have described systemic delivery of the veratrum alkaloid for prompting baroreflex actions. While use of veratrum alkaloids originally appeared quite promising, numerous deleterious side effects associated with systemic application of the compound, such as nausea and severe hypotension, rendered the therapy minimally useful. In short, compound toxicity and related side effects have limited clinical utility of veratrum alkaloids.
Treatment of cardiovascular disorders characterized by increased heart rate or blood pressure, such as hypertension or congestive heart failure, by neural stimulation presents a highly viable therapy. To this end, while electrical stimulation via an implanted electrode is effective, certain potential disadvantages have been identified. Alternatively, systemic delivery of chemical nerve stimulators, and in particular veratrum alkaloids, has been problematic. Therefore, a substantial need exists for a neural stimulation device configured to deliver a nerve stimulating drug, such as veratrum alkaloid, directly to a nerve in conjunction with electrical nerve stimulation.